Among the 2.5 million breast cancer survivors in the U.S. more than 40% of them have developed lymphedema (LE). Post-breast cancer LE, a syndrome of abnormal swelling and multiple distressing symptoms, is caused by injuries to the lymphatic system from cancer treatment. As advances in cancer treatment lengthen survival, LE has emerged as a high-impact long-term morbidity that profoundly impairs survivors'quality of life. All women undergoing breast cancer treatment are at lifetime risk for LE. While removal of lymph nodes, surgery, and radiation are the major causal factors for LE, cancer treatment is necessary for life-saving. Recent research has revealed that inflammation-infection and higher body mass index (BMI) are the main predictors of LE besides treatment-related risk. Unfortunately, these studies did not evaluate biomarkers known for inflammation, and thus the role of inflammation-infection in limb volume change (LVC) and LE development could not be ascertained. Elevated levels of proinflammatory biomarkers have been speculated to be associated with inflammation in patients with LE. Moreover, genetic variations may be one of the important factors that influence breast cancer survivors'responses to inflammatory processes and vulnerability to LE, including survivors'responses to treatment-related trauma (such as surgery and radiation) and triggering factors (such as infection, burns, minor injuries, and higher BMI or obesity). The purpose of this exploratory project is to prospectively examine levels and patterns of proinflammatory biomarkers and genetic variations in relation to LVC measured with the infra-red perometer-400T/350S over a 12-month period in breast cancer survivors who are at risk for LE. The project will employ a prospective, descriptive, and repeated-measure design. A sample of 120 women who are newly diagnosed and treated for invasive breast cancer will be recruited. Data will be collected over a 12-month period, including: (1) measuring and comparing LVC using the infra-red perometer, LE symptoms, BMI and body composition;(2) evaluating levels and patterns of proinflammatory biomarkers in relation to LVC;and (3) evaluating genotypes known for inflammation in relation to LVC. These proinflammatory biomarkers and candidate genes include lymphatic specific growth factors (VEGF-C &VEGF-D), cytokines (IL1-a, IL1-b, IL6, IL8, &IL10), and tumor necrosis factor-a. This project is an important first step toward gaining necessary knowledge and insights into breast cancer survivors'susceptibility, which may help to identify survivors at higher risk based on individual survivors'biomarker patterns and genetic factors. Findings of the project are fundamental in developing and testing more intense and personalized interventions to prevent and treat LE among the breast cancer survivors. PUBLIC HEALTH RELEVANCE: Lymphedema, a syndrome of abnormal swelling and multiple distressing symptoms, is a major adverse effect of breast cancer treatment, which can cause long-term physical, psychological, social, and financial problems. The purpose of this exploratory project is to prospectively examine levels and patterns of proinflammatory biomarkers and genetic variations in relation to limb volume changes measured with the infra-red perometer- 400T/350S over a 12-month period in breast cancer survivors. This project is an important first step toward gaining necessary knowledge and insights into breast cancer survivors'susceptibility, which may help to identify survivors at higher risk based on individual survivors'biomarker patterns and genetic factors and potentially target the survivors at higher risk for more intense and personalized interventions to prevent and treat lymphedema.